Association of the systemic host immune response with acute hyperglycemia in mechanically ventilated septic patients.
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ABSTRACT:
SUBMITTER: Farooq N
PROVIDER: S-EPMC7987165 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Rationale: Patients in the intensive care unit (ICU) are frequently exposed to unnecessary antibiotics. Markers of the host response to infection may aid pneumonia diagnosis and avoid antibiotic-induced complications. Objective: To assess the host response to suspected bacterial pneumonia through assessment of alveolar neutrophilia and transcriptomic profiling of alveolar macrophages. Methods: We determined the test characteristics of BAL neutrophilia for the diagnosis of bacterial pneumonia in 3 cohorts of mechanically ventilated patients. In one cohort, we also isolated alveolar macrophages from BAL fluid and used the transcriptome to identify signatures of bacterial pneumonia. Finally, we developed a humanized mouse model of Pseudomonas aeruginosa pneumonia to determine if pathogen-specific signatures can be identified in human alveolar macrophages. Measurements and Main Results: BAL neutrophilia was highly sensitive for bacterial pneumonia in both the retrospective (N = 851) and validation cohorts (N = 76 and N = 79) with a negative predictive value of over 90% when BAL neutrophil percentage was less than 50%. A transcriptional signature of bacterial pneumonia was present in both resident and recruited macrophages. Gene signatures from both cell types identified patients with bacterial pneumonia with test characteristics similar to BAL neutrophilia. Conclusions: A BAL neutrophil percentage of less than 50% is highly sensitive for bacterial pneumonia. Informative transcriptomic signatures can be generated from BAL fluid obtained during routine clinical care in the ICU. The identification of novel host response biomarkers is a promising approach to aid the diagnosis and treatment of pneumonia.
2018-11-06 | GSE121871 | GEO
Project description:Mechanically ventilated surgical patients have a variety of bacterial flora that are often undetectable by traditional culture methods. The source of infection in many of these patients remains unclear. To address this clinical problem, the microbiome profile and host inflammatory response in bronchoalveolar lavage samples from the surgical intensive care unit were examined relative to clinical pathology diagnoses. The hypothesis was tested that clinical diagnosis of respiratory tract flora were similar to culture positive lavage samples in both microbiome and inflammatory profile. Bronchoalveolar lavage samples were collected in the surgical intensive care unit as standard of care for intubated individuals with a clinical pulmonary infection score of >6 or who were expected to be intubated for >48 hours. Cytokine analysis was conducted with the Bioplex Pro Human Th17 cytokine panel. The microbiome of the samples was sequenced for the 16S rRNA region using the Ion Torrent. Microbiome diversity analysis showed the culture-positive samples had the lowest levels of diversity and culture negative with the highest based upon the Shannon-Wiener index (culture positive: 0.77 ± 0.36, respiratory tract flora: 2.06 ± 0.73, culture negative: 3.97 ± 0.65). Culture-negative samples were not dominated by a single bacterial genera. Lavages classified as respiratory tract flora were more similar to the culture-positive in the microbiome profile. A comparison of cytokine expression between groups showed increased levels of cytokines (IFN-g, IL-17F, IL-1B, IL-31, TNF-a) in culture-positive and respiratory tract flora groups. Culture-positive samples exhibited a more robust immune response and reduced diversity of bacterial genera. Lower cytokine levels in culture-negative samples, despite a greater number of bacterial species, suggest a resident nonpathogenic bacterial community may be indicative of a normal pulmonary environment. Respiratory tract flora samples were most similar to the culture-positive samples and may warrant classification as culture-positive when considering clinical treatment.
| S-EPMC6200244 | biostudies-literature
Project description:BackgroundGlucocorticoids are commonly used in patients with or at-risk for acute respiratory distress syndrome (ARDS), but optimal use remains unclear despite well-conducted clinical trials. We performed a secondary analysis in patients previously enrolled in the Acute Lung Injury and Biospecimen Repository at the University of Pittsburgh. The primary aim of our study was to investigate early changes in host response biomarkers in response to real-world use of glucocorticoids in patients with acute respiratory failure due to ARDS or at-risk due to a pulmonary insult. Participants had baseline plasma samples obtained on study enrollment and on follow-up 3 to 5 days later to measure markers of innate immunity (IL-6, IL-8, IL-10, TNFr1, ST2, fractalkine), epithelial injury (sRAGE), endothelial injury (angiopoietin-2), and host response to bacterial infections (procalcitonin, pentraxin-3). In our primary analyses, we investigated the effect of receiving glucocorticoids between baseline and follow-up samples on host response biomarkers measured at follow-up by doubly robust inverse probability weighting analysis. In exploratory analyses, we examined associations between glucocorticoid use and previously characterized host response subphenotypes (hyperinflammatory and hypoinflammatory).Results67 of 148 participants (45%) received glucocorticoids between baseline and follow-up samples. Dose and type of glucocorticoids varied. Regimens that used hydrocortisone alone were most common (37%), and median daily dose was equivalent to 40 mg methylprednisolone (interquartile range: 21, 67). Participants who received glucocorticoids were more likely to be female, to be on immunosuppressive therapy at baseline, and to have higher baseline levels of ST-2, fractalkine, IL-10, pentraxin-3, sRAGE, and TNFr1. Glucocorticoid use was associated with decreases in IL-6 and increases in fractalkine. In exploratory analyses, glucocorticoid use was more frequent in participants in the hyperinflammatory subphenotype (58% vs 40%, p = 0.05), and was not associated with subphenotype classification at the follow-up time point (p = 0.16).ConclusionsGlucocorticoid use varied in a cohort of patients with or at-risk for ARDS and was associated with early changes in the systemic host immune response.
| S-EPMC10914652 | biostudies-literature
Project description:IntroductionRight ventricle (RV) dilation in combination with elevated central venous pressure (CVP), which is a state of RV congestion, is seen as a sign of RV failure (RVF). On the other hand, RV systolic function is usually assessed by tricuspid annular plane systolic excursion (TAPSE) and fractional area change (FAC). This study aimed to investigate the prevalence and prognostic value of RVF and RV systolic dysfunction (RVSD) in septic patients.MethodsMechanically ventilated sepsis and septic shock patients were included. We collected haemodynamic and echocardiographic parameters as well as prognostic information including mechanical ventilation duration, length of ICU stay and 30-day mortality. RVF was defined as a right and left ventricular end-diastolic area ratio ≥ 0.6 in combination with CVP ≥ 8 mmHg. RVSD was defined as TAPSE < 16 mm or FAC < 35%.ResultsA total of 215 patients were enrolled in this study, and the patients were divided into 4 groups: patients with normal RV function (normal, n = 101), patients with RVF but without RVSD (RVF only, n = 38), patients with RVSD but without RVF (RVSD only, n = 44), and patients with combined RVF-RVSD (RVF/RVSD, n = 32). The RVF/RVSD group and RVSD only group had a lower cardiac index than the RVF only group and normal groups (p < 0.05). At 30 days after ICU admission, 50.0% of patients had died in the RVF/RVSD group, which was much higher than the mortality in the RVF only group (13.2%) and normal group (13.9%) (p < 0.05). In a Cox regression analysis, the presence of RVF/RVSD was independently associated with 30-day mortality (HR 3.004, 95% CI:1.370-6.587, p = 0.006). In contrast, neither the presence of RVF only nor the presence of RVSD only was associated with 30-day mortality (HR 0.951, 95% CI:0.305-2.960, p = 0.931; HR 1.912, 95% CI:0.853-4.287, p = 0.116, respectively).ConclusionThe presence of combined RVF-RVSD was associated with 30-day mortality in mechanically ventilated septic patients. Additional studies are needed to confirm and expand this finding.
| S-EPMC8276910 | biostudies-literature
Project description:The impact of extrapulmonary organ dysfunction, independent from sepsis and lung injury severity, on outcomes in pediatric acute respiratory failure is unclear. We sought to determine the frequency, timing, and risk factors for extrapulmonary organ dysfunction and the independent association of multiple organ dysfunction syndrome with outcomes in pediatric acute respiratory failure.Secondary observational analysis of the Randomized Evaluation of Sedation Titration for Respiratory Failure cluster-randomized prospective clinical trial conducted between 2009 and 2013.Thirty-one academic PICUs in the United States.Two thousand four hundred forty-nine children mechanically ventilated for acute respiratory failure enrolled in Randomized Evaluation of Sedation Titration for Respiratory Failure.Organ dysfunction was defined using criteria published for pediatric sepsis. Multiple organ dysfunction syndrome was defined as respiratory dysfunction one or more extrapulmonary organ dysfunctions. We used multivariable logistic regression to identify risk factors for multiple organ dysfunction syndrome, and logistic or proportional hazards regression to compare clinical outcomes. All analyses accounted for PICU as a cluster variable. Overall, 73% exhibited extrapulmonary organ dysfunction, including 1,547 (63%) with concurrent multiple organ dysfunction syndrome defined by onset on day 0/1 and 244 (10%) with new multiple organ dysfunction syndrome with onset on day 2 or later. Most patients (93%) with indirect lung injury from sepsis presented with concurrent multiple organ dysfunction syndrome, whereas patients with direct lung injury had both concurrent (56%) and new (12%) multiple organ dysfunction syndrome. Risk factors for concurrent multiple organ dysfunction syndrome included older age, illness severity, sepsis, cancer, and moderate/severe lung injury. Risk factors for new multiple organ dysfunction syndrome were moderate/severe lung injury and neuromuscular blockade. Both concurrent and new multiple organ dysfunction syndrome were associated with 90-day in-hospital mortality (concurrent: adjusted odds ratio, 6.54; 95% CI, 3.00-14.25 and new: adjusted odds ratio, 3.21; 95% CI, 1.48-6.93) after adjusting for sepsis, moderate/severe lung injury, and other baseline characteristics.Extrapulmonary organ dysfunction was common, generally occurred concurrent with respiratory dysfunction (especially in sepsis), and was a major risk factor for mortality in pediatric acute respiratory failure.
| S-EPMC5380520 | biostudies-literature
Project description: Not available
| S-EPMC11198220 | biostudies-literature
Project description:To better describe the outcomes of acute respiratory distress syndrome in mechanically ventilated patients with cirrhosis.DesignSingle-center, retrospective study of mechanically ventilated patients with cirrhosis between 2008 and 2015.SettingICU at a large academic medical and transplant center.PatientsOne hundred eighty-one mechanically ventilated patients with cirrhosis.InterventionsDemographic and clinical data were reviewed, and acute respiratory distress syndrome was identified per Berlin criteria. We compared demographic and clinical characteristics on ICU admission in patients with and without acute respiratory distress syndrome. The primary endpoint was hospital mortality (including discharge to hospice). Mortality risk was stratified by Chronic Liver Failure-Sequential Organ Failure Assessment and Model for End-Stage Liver Disease.Measurements and main resultsThe mean age in 181 eligible patients was 53 ± 11 years; 67% were male; and 91% were Caucasian. In all, n = 35 (19%) of mechanically ventilated patients had acute respiratory distress syndrome. They were more frequently female (46% vs 30%; p = 0.08), with suspected infection (86% vs 53%; p < 0.001), and had higher mean Model for End-Stage Liver Disease (32 vs 24; p < 0.001) and Chronic Liver Failure-Sequential Organ Failure Assessment (15 vs 11; p < 0.001) than patients without acute respiratory distress syndrome. Hospital mortality was higher in patients with (40%) versus without (22%) acute respiratory distress syndrome (p = 0.03). In the risk-adjusted analysis (for Model for End-Stage Liver Disease, Chronic Liver Failure-Sequential Organ Failure Assessment and age), acute respiratory distress syndrome was not independently associated with hospital mortality (odds ratio, 0.80; CI, 0.3-2.5; p = 0.7).ConclusionsAcute respiratory distress syndrome is common in mechanically ventilated patients with cirrhosis but is not independently associated with increased mortality.
| S-EPMC7063938 | biostudies-literature
Project description:Hypercapnia resulting from protective ventilation in acute respiratory distress syndrome triggers metabolic pH compensation, which is not entirely characterized. We aimed to describe this metabolic compensation.The data were retrieved from a prospective collected database. Variables from patients' admission and from hypercapnia installation until the third day after installation were gathered. Forty-one patients with acute respiratory distress syndrome were analyzed, including twenty-six with persistent hypercapnia (PaCO2 > 50mmHg > 24 hours) and 15 non-hypercapnic (control group). An acid-base quantitative physicochemical approach was used for the analysis.The mean ages in the hypercapnic and control groups were 48 ± 18 years and 44 ± 14 years, respectively. After the induction of hypercapnia, pH markedly decreased and gradually improved in the ensuing 72 hours, consistent with increases in the standard base excess. The metabolic acid-base adaptation occurred because of decreases in the serum lactate and strong ion gap and increases in the inorganic apparent strong ion difference. Furthermore, the elevation in the inorganic apparent strong ion difference occurred due to slight increases in serum sodium, magnesium, potassium and calcium. Serum chloride did not decrease for up to 72 hours after the initiation of hypercapnia.In this explanatory study, the results indicate that metabolic acid-base adaptation, which is triggered by acute persistent hypercapnia in patients with acute respiratory distress syndrome, is complex. Furthermore, further rapid increases in the standard base excess of hypercapnic patients involve decreases in serum lactate and unmeasured anions and increases in the inorganic apparent strong ion difference by means of slight increases in serum sodium, magnesium, calcium, and potassium. Serum chloride is not reduced.
| S-EPMC4828087 | biostudies-other
Project description:BackgroundProne positioning improves survival in moderate-to-severe acute respiratory distress syndrome (ARDS) unrelated to the novel coronavirus disease (COVID-19). This benefit is probably mediated by a decrease in alveolar collapse and hyperinflation and a more homogeneous distribution of lung aeration, with fewer harms from mechanical ventilation. In this preliminary physiological study we aimed to verify whether prone positioning causes analogue changes in lung aeration in COVID-19. A positive result would support prone positioning even in this other population.MethodsFifteen mechanically-ventilated patients with COVID-19 underwent a lung computed tomography in the supine and prone position with a constant positive end-expiratory pressure (PEEP) within three days of endotracheal intubation. Using quantitative analysis, we measured the volume of the non-aerated, poorly-aerated, well-aerated, and over-aerated compartments and the gas-to-tissue ratio of the ten vertical levels of the lung. In addition, we expressed the heterogeneity of lung aeration with the standardized median absolute deviation of the ten vertical gas-to-tissue ratios, with lower values indicating less heterogeneity.ResultsBy the time of the study, PEEP was 12 (10-14) cmH2O and the PaO2:FiO2 107 (84-173) mmHg in the supine position. With prone positioning, the volume of the non-aerated compartment decreased by 82 (26-147) ml, of the poorly-aerated compartment increased by 82 (53-174) ml, of the normally-aerated compartment did not significantly change, and of the over-aerated compartment decreased by 28 (11-186) ml. In eight (53%) patients, the volume of the over-aerated compartment decreased more than the volume of the non-aerated compartment. The gas-to-tissue ratio of the ten vertical levels of the lung decreased by 0.34 (0.25-0.49) ml/g per level in the supine position and by 0.03 (- 0.11 to 0.14) ml/g in the prone position (p < 0.001). The standardized median absolute deviation of the gas-to-tissue ratios of those ten levels decreased in all patients, from 0.55 (0.50-0.71) to 0.20 (0.14-0.27) (p < 0.001).ConclusionsIn fifteen patients with COVID-19, prone positioning decreased alveolar collapse, hyperinflation, and homogenized lung aeration. A similar response has been observed in other ARDS, where prone positioning improves outcome. Therefore, our data provide a pathophysiological rationale to support prone positioning even in COVID-19.
| S-EPMC9076814 | biostudies-literature
Project description:ObjectivesTo determine why non-mechanically ventilated hospitalized older adults are transferred to long-term acute care (LTAC) hospitals rather than remaining in the hospital.DesignObservational cohort.SettingNational Medicare data.ParticipantsNon-mechanically ventilated hospitalized adults aged 65 and older with fee-for-service Medicare in 2012 who were transferred to an LTAC hospital (n=1,831) or had a prolonged hospitalization without transfer (average hospital length of stay or longer of those transferred to an LTAC hospital) and had one of the 50 most common hospital diagnoses leading to LTAC transfer (N=12,875).MeasurementsWe assessed predictors of transfer using a multilevel model, adjusting for patient-, hospital-, and hospital referral region (HRR)-level factors. We estimated proportions of variance at each level and adjusted hospital- and HRR-specific LTAC transfer rates using sequential models.ResultsThe strongest predictor of transfer was being hospitalized near an LTAC hospital (<1.4 vs > 33.6 miles, adjusted odds ratio=6.2, 95% confidence interval (CI)=4.2-9.1). After adjusting for case mix, differences between hospitals explained 15.4% of the variation in LTAC use and differences between regions explained 27.8%. Case mix-adjusted LTAC use was high in the South, where many HRRs had rates between 20.3% and 53.1%, whereas many HRRs were less than 5.4% in the Pacific Northwest, North, and New England. From our fully adjusted model, the median adjusted hospital LTAC transfer rate was 7.2% (interquartile range 2.8-17.5%), with substantial within-region variation (intraclass coefficient=0.25, 95% CI=0.21-0.30).ConclusionsNearly half of the variation in LTAC use is independent of illness severity and is explained by which hospital and what region the individual was hospitalized in. Because of the greater fragmentation of care and Medicare spending with LTAC transfers (because LTAC hospitals generate a separate bundled payment from the hospital), greater attention is needed to define the optimal role of LTAC hospitals in caring for older adults. J Am Geriatr Soc 66:2112-2119, 2018.
| S-EPMC6239216 | biostudies-literature